The blood clotting process consists of several of the most important types of reactions in protein chemistry, viz., enzymatic steps (proteolysis, transamidation, etc.) and protein association. In this project, we are concentrating on the proteolytic action of thrombin on fibrinogen. We thus hope to contribute to an understanding of the mechanism of this fundamental protein reaction, as it is involved in the blood clotting process, and, at the same time, to provide a basis for treating some of the cardio-vascular problems involving blood clotting (eg., heart failure, stroke, hemophilia, etc.) The mechanism of the action of thrombin on fibrinogen is being investigated by active-site mapping (kinetics of hydrolysis of Arg-Gly bonds of natural and synthetic fibrinogen-like substrates), spectroscopic (NMR, ESR and Raman), photochemical, and immunochemical studies of the conformations of the interacting species of the enzyme-substrate complexes, studies of the effect of chemical modification of thrombin on its enzymatic activity, and immunochemical-electron microscope study of the thrombin-fibrinogen interaction.